> > The effect acts both mechanically [altering K+
> concentration within glia alters glial Geometry,
> which alters neural Geometry, including synaptic
> 'pressures', etc.], and conductance-dynamically
> [altering passive spreading, action potential
> thresholds, etc.],
Yep. That is all well established. There is considerable evidence
suggesting that oligodendroglia exhibit rhythmic pulsatile movements that
may be responsible for regulating the infraslow potentials (i.e. 2-5 min)
generated by the brain. Theories implementing glial cells in learning, etc.,
have been presented in the 30's and 40's. It's a fascinating area of
research and I agree with you that perhaps more active roles are involved
with these cells.
Read some of Jim Roberston's work on the subject. He has an interesting
paper published in Journal of Physiology a few years ago (2002) on the
subject. And Perea and Araque published an extremely interesting paper on
the potential dynamic communication between neurons and astrocytes. It was
also published in J. Physiology and in the same issue as well. (An issue
that as you expected reviewed glial cells and their involvement in the
nervous system.) (more below).
> And this position is Testable.
>
> The necessary experimental design has to present
> experimental subjects with the opportunity to
> acquire, and switch between, widely-differentiated,
> robustly-established memory 'states'.
>> Train to task, then train to widely-differentiated
> task. Then, present one task or the other, and
> sacrifice at various stages of 'switching' [which can
> be monitored by measures that quantify completeness
> of 'memory state' switching.
Yes. There are a many paradigms that can be done to test this aspect of
"switching". There are many hippocampal pattern recognition tasks could be
used.
>> If NDT's position is Correct [it is :-], then there'll be
> observable glial anion differentiation that's correlated
> with 'memory state'.
> What happens is [I expect] that glial anion 'conforma-
> tions' are tunable, and this affects both glial structural-
> 'conformation' and glial K+ conductance in a way that's
> correlated to 'memory state', and which can vary
> Profoundly, with respect to different neurons, none of
> which does the "Nernst Equation" see, or allow for.
I don't buy the K+ component you are advocating simply because this has
already been well studied and the results aren't all that impressive.
Simply put, the range of encoding that would accompany both K+ influx and
efflux is not sufficiently dynamic and broad enough to serve as
communicative template to provide any meaningful information for a neuron.
I doubt you would find a correlated memory state based upon the
intracellular levels of potassium. K+ doesn't elevate as much as what you
are think it does in the normal brain. Your best bet would be to
concentrate your theory on calcium oscillations. Carmagnto(?) has shown the
importance of these processes within astrocytes. Moreover, calcium
oscillations have been shown to regulate the release of glial-related
proteins, that could serve as modulatory in synaptic efficacy and important
for the regulation of long-lasting potentation.
If, glial cells play a role, it would be a dynamic and modulatory role on
neuronal functioning. Glial cells DO NOT (or shall say, HAVE NOT BEEN
SHOWN) to play a direct role in memory consolidation. Their role is simply
to modulate neuronal transmission. Two recent studies may be of interest to
you. One study showed that activation of working memory networks was
significantly correlated with the extent of glial cell activation and
metabolites in HIV brain injured patients (which exhibit abnormal glial
inflammatory effects). They hypothesized that the increased glial
processing is associated with a decrease in neuronal processing. A
second study (published in PNAS) showed that astrocytes synthesize an
important calcium binding protein, S-100B. It is believed that astrocytes
release this protein extracellularly and that it can modulate neuronal
functioning. Mice devoid of S-100B exhibit greater synaptic plasticity and
enhanced learning.
These points suggest that glial cells are not directly involved with
learning and memory consolidation per se, but instead regulate the activity
of neuronal elements that are important for the long-term maintenance of
information. The memory state, as you suggest, would not be associated with
glial cells directly but instead would reflect the role of glial cells in
regulating the operations of neurons in a dynamic manner. Considering the
strong electrotonic coupling that exists between glial cells, the syncytium
nature of glial cells could be instrumental in orchestrating perturbation in
neuronal firing dynamics in such a matter that profound shifts in cognitive
processes may occur. In light of Pribrim concept on the holographic
representation of memory within the brain, glial cells and glial processes
may be useful for producing the interference patterns that can be
superimposed upon the background activity of the brain. Enhancing the
contrast between electrical patterns of experience and background patterns
of activity.
(However, there is a cautionary note. Older studies have shown that the
actual oscillatory shifts exhibited by glial cells are on a time scale that
is too large to play any direct or active role in modulating complex
cognitive processes. Simply put, if glial cells are going to play the
complex and global role in producing memory state switches, some other
mechanism besides current models on neuronal signaling must be shown. )